During certain surgical procedures, neuromuscular blocking agents must be employed. However, neuromuscular blocking agents literally paralyze a patient for the time during which they are active. Hence, the use of neuromuscular blocking agents is restricted to situations where muscle relaxation is essential for effective treatment of a patient, for example, selected surgical procedures involving intubation of the trachea. Because paralysis can interfere with essential body functions (e.g. breathing) the physician selects a neuromuscular blocking agent that will be active for as long as needed but no more than is needed. For example, when a breathing tube must be inserted into the trachea of a patient, a neuromuscular blocking agent is used to relax the tracheal muscles and permit intubation. However, the neuromuscular blocking agent also relaxes the muscles of the chest, thereby causing the patient to stop breathing. The anesthesiologist must quickly insert the breathing tube into the patient's trachea and begin ventilation of the lungs. If the tube cannot be inserted quickly enough, the physician must intervene with some form of artificial resuscitation or the patient may suffer oxygen deprivation, and the associated tissue and brain damage that may result from lack of oxygen. Fast reversal of the neuromuscular blocking agent by a rapidly acting antagonist can remove the patient from danger and avoid, or minimize, the duration of artificial resuscitation.
The inventors have developed neuromuscular blocking agents that, surprisingly, are quickly reversed by injection of a thiol such as the amino acid, cysteine. However, physiological cysteine solutions at useful concentrations are unstable and easily oxidize or dimerize.